Respiratory syncytial virus (RSV)-caused disease represents a significant health care burden worldwide. The RSV infects virtually all children throughout the world in both developed and developing countries. Re-infection is common because natural infection does not induce lasting immunity. Also, severe RSV infections are increasingly occurring among the elderly. In spite of wide-scale efforts to produce an effective vaccine against RSV, no vaccine is yet available. Development of an inexpensive edible plant-based oral vaccine is an innovative approach for the control of RSV. The present study extends the strategy of using a plant-based oral vaccine to a respiratory pathogen for the first time. Even if lasting immunity is not obtained with the plant-based vaccine, it would be relatively low in cost to use such a vaccine during successive RSV seasons. We have shown previously that oral immunization of mice with transgenic tomato fruit expressing an RSV- subunit protein, i.e., the F-protein, induces a systemic immune response. This "proof of principle" Phase I study will optimize the expression of the RSV-F protein in the transgenic tomato fruit and determine the capacity of this orally-given antigenic protein to protect against an RSV challenge in two commonly-used models for RSV studies, the Balb/c mouse and the cotton rat. Success will validate the further development of our tomato- based vaccine against RSV and set the stage for a Phase II study. Such a vaccine will definitely make a difference and have an enduring impact on human health. PUBLIC HEALTH RELEVANCE: Respiratory syncytial virus-caused disease is a significant health care burden worldwide, but no vaccine is available. We are developing an inexpensive vaccine using tomato plants to control this virus.